A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells

Hyun Ju Lee, Deniz Bartsch, Cally Xiao, Santiago Guerrero, Gaurav Ahuja, Christina Schindler, James J. Moresco, John R. Yates, Fátima Gebauer, Hisham Bazzi, Christoph Dieterich, Leo Kurian and David Vilchez ()
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Hyun Ju Lee: University of Cologne
Deniz Bartsch: University of Cologne
Cally Xiao: University of Cologne
Santiago Guerrero: Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology
Gaurav Ahuja: University of Cologne
Christina Schindler: University of Cologne
James J. Moresco: 10550 North Torrey Pines Road, SR111, The Scripps Research Institute
John R. Yates: 10550 North Torrey Pines Road, SR111, The Scripps Research Institute
Fátima Gebauer: Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology
Hisham Bazzi: University of Cologne
Christoph Dieterich: Department of Internal Medicine III and Klaus Tschira Institute for Computational Cardiology, Neuenheimer Feld 669, University Hospital
Leo Kurian: University of Cologne
David Vilchez: University of Cologne

Nature Communications, 2017, vol. 8, issue 1, 1-19

Abstract: Abstract While the transcriptional network of human embryonic stem cells (hESCs) has been extensively studied, relatively little is known about how post-transcriptional modulations determine hESC function. RNA-binding proteins play central roles in RNA regulation, including translation and turnover. Here we show that the RNA-binding protein CSDE1 (cold shock domain containing E1) is highly expressed in hESCs to maintain their undifferentiated state and prevent default neural fate. Notably, loss of CSDE1 accelerates neural differentiation and potentiates neurogenesis. Conversely, ectopic expression of CSDE1 impairs neural differentiation. We find that CSDE1 post-transcriptionally modulates core components of multiple regulatory nodes of hESC identity, neuroectoderm commitment and neurogenesis. Among these key pro-neural/neuronal factors, CSDE1 binds fatty acid binding protein 7 (FABP7) and vimentin (VIM) mRNAs, as well as transcripts involved in neuron projection development regulating their stability and translation. Thus, our results uncover CSDE1 as a central post-transcriptional regulator of hESC identity and neurogenesis.

Date: 2017
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DOI: 10.1038/s41467-017-01744-5

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